Studies On The Synthesis Of Chiral Vicinal Amino Alcohols And Related Pharmaceuticals

Vicinal amino alcohols are an important class of compounds . With the development of chiral compounds, chiral vicinal amino alcohols are widely . (S)-2-amino-1-propanol, (S)-2-amino-1-butanol and Related Pharmaceuticals were investigated in this paper. The synthesis of (S)-(+)-2-amino-1-propanol and Levofloxacin were investigated in this paper. The main work was described as following:(R,S)-2-amino-1-propanol was obtained from propylene oxide through treatment of propylene oxide with ammonia, esterification and cyclization with sulfuric acid and ring opening reaction with phthalic anhydride. Furthermore 2-amino-1-propanol was prepared in 72% yield from condensation of nitroethyane and formaldehyde, followed by hydrogenation with Raney Ni.(S)-(+)-2-amino-1-propanol was prepared in 84.7% yield by the reduction of ethyl L-alaninate with sodium borohydride, the reaction parameters were optimized.KBH4 was modified with ZnCl2, and employed as reducing agent for reduction of ethyl L-alaninate to afford (S)-(+)-2-amino-1-propanol in 60.2%.Sodium and BER resin were separately used to reduce ethyl L-alaninate to produce (S)-(+)-2-amino-1-propanol in 45.1% and 32.6% yield.Levofloxacin was synthesized in 14.1% total yield from 2,3,4,5-tetrafluoro-benzoic acid and the synthetic procedures were optimized. A series of derivatives of Levofloxacin were prepared for biological activities test.The synthesis of ethambutol hydrochloride used as an antituberculosis agent, was studied systematically in this paper, including the synthesis and resolution of (R,S)-2-aminobutanol, racemization of (R)-2-aminobutanol and the recovery of L-(+)-tartaric acid. The (R,S)-2-aminobutanol was synthesized from 1-butene, chlorine and acetonitrile in a yield of over 25%. The (S)-2-aminobutanol L-(+)-tartrate was obtained from the resolution of (R,S)-2-aminobutanol with L-(+)-tartaric acid in 94% yield, and (R)-2-aminobutanol L-(+)-tartrate was recovered in 99% yield by the treatment of the filtrate. The optically pure (S)-2-aminobutanol and (R)-2-aminobutanol were obtained over 85% yield by the hydrolysis of two 2-aminobutanol L-(+)-tartrate isomers separately. In the presence of racemization of (R)-2-aminobutanol proceeds effectively of Raney Ni to afford (R,S)-2-aminobutanol in a yield of over 70%. The mixtures have no optical rotation. The L-(+)-tartaric acid was recovered over 70% yield from sodium tartrate which was obtained through the hydrolysis of (R,S)-2-aminobutanol L-(+)-tartrate. What's more, the synthesis of ethambutol from (S)-2-aminobutanol and 1,2-dichloroethane was investigated intensively. The process parameters, such as the ratio of starting materials and the reaction time, were optimized. Thus, the optically pure ethambutol was obtained in 81.25% yield under the optimum reaction conditions.